PARADISE-MI clinical trial review

PARADISE-MI clinical trial review

Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) aimed at checking whether sacubitril/valsartan reduces cardiovascular death following high-risk acute myocardial infarction compared to angiotensin-converting enzyme inhibitor [1]. PARADIGM-HF trial had shown that sacubitril-valsartan reduces risk of hospitalization for heart failure and death from cardiovascular causes more effectively than ACE inhibitors in patients with symptomatic chronic heart failure with reduced ejection fraction [2]. But these drugs had not been compared in the setting of acute myocardial infarction.

PARADISE-MI was in patients with myocardial infarction with reduced left ventricular ejection fraction, pulmonary congestion or both. Primary outcome evaluated was death from cardiovascular causes or incident heart failure, which ever occurred first. Of the total 5661 patients randomized, 2830 were assigned to sacubitril-valsartan and 2831 to ramipril. Primary outcome event occurred in 338 of the sacubitril-valsartan group and 373 of the ramipril group, over a median follow up period of 22 months. Death from cardiovascular causes occurred in 168 patients in the ARNI group and 191 patients in the ramipril group. Authors concluded that sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction [2].

Thus PARADISE-MI may be considered as a neutral trial. Authors claimed that the trial had sufficient power to detect the treatment effect size they had anticipated. Overall incidence of adverse effects which can be attributed to the trial therapy was similar in both groups and so was the safety profile. More discontinuation of medication due to hypotension was seen in ARNI group while more discontinuation due to cough was noted in ramipril group, as expected.

References

1. Jering KS, Claggett B, Pfeffer MA, Granger C, Køber L, Lewis EF, Maggioni AP, Mann D, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, van der Meer P, Wernsing M, Carter K, Guo W, Zhou Y, Lefkowitz M, Gong J, Wang Y, Merkely B, Macin SM, Shah U, Nicolau JC, Braunwald E. Prospective ARNI vs. ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): design and baseline characteristics. Eur J Heart Fail. 2021 Jun;23(6):1040-1048. doi: 10.1002/ejhf.2191. Epub 2021 Apr 22. PMID: 33847047.
2. McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30. PMID: 25176015.
3. Pfeffer MA, Claggett B, Lewis EF, Granger CB, Køber L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, East C, Fernandez A, Jering K, Landmesser U, Mehran R, Merkely B, Vaghaiwalla Mody F, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Gong J, Braunwald E; PARADISE-MI Investigators and Committees. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction. N Engl J Med. 2021 Nov 11;385(20):1845-1855. doi: 10.1056/NEJMoa2104508. Erratum in: N Engl J Med. 2021 Dec 30;385(27):2592. PMID: 34758252.